RIG-I and TLR3 are both required for maximum interferon induction by influenza virus in human lung alveolar epithelial cells

Virology. 2015 Aug;482:181-8. doi: 10.1016/j.virol.2015.03.048. Epub 2015 Apr 11.

Abstract

Pattern recognition receptors, such as retinoic acid-inducible protein I (RIG-I), Toll-like receptors 3 and 7 (TLR3 and 7), and nucleotide-binding oligomerization domain containing protein 2 (NOD2), play important roles in the recognition of influenza A virus (IAV), but their role in interferon (IFN) induction is still unclear, particularly in human lung. We investigated IFN induction by IAV in the A549 cell line as well as in primary human alveolar epithelial cells (AEC). TLR3/7, NOD2, RIG-I, and IFN expression levels were measured by qRT-PCR and ELISA in cells infected with IAV PR8. We found that TLR7 and NOD2 were not involved in IFN induction by IAV in these cells. Neither RIG-I nor TLR3 siRNA alone completely blocked IFN induction. However, double knockdown of RIG-I and TLR3 completely inhibited IFN induction by influenza. Thus, signaling through both RIG-I and TLR3 is important for IFN induction by IAV in human lung AEC.

Keywords: A549; AEC; Human; Influenza; Innate immunity; Interferon; Lung; PR8; RIG-I; TLR3.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Cells, Cultured
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / metabolism*
  • Enzyme-Linked Immunosorbent Assay
  • Epithelial Cells / immunology*
  • Epithelial Cells / virology*
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Humans
  • Influenza A Virus, H1N1 Subtype / immunology*
  • Interferons / metabolism*
  • Real-Time Polymerase Chain Reaction
  • Toll-Like Receptor 3 / metabolism*

Substances

  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Interferons
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases